Pharmacokinetic and pharmacodynamic interaction study between midazolam and the macrolide antibiotics, erythromycin, clarithromycin, and the azalide azithromycin.
This report includes a recalculation of the pooled data of 2 pharmacokinetic and pharmacodynamic studies of the interaction between the hypnotic midazolam and the antibiotics erythromycin, clarithromycin (macrolides), and azithromycin (an azalide). Erythromycin and clarithromycin similarly and strikingly impaired the metabolism of midazolam and enhanced its pharmacodynamic activity; little or no effect was found with azithromycin. It was concluded that coadministration of midazolam and azithromycin involves less clinical risk than with the 2 macrolides.
Yeates
R A
RA
Department of Pharmacology, Pfizer-Mack Development Center, Illertissen, Germany.
Laufen
H
H
Zimmermann
T
T
Schumacher
T
T
D014151:Anti-Anxiety Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D019540:Area Under Curve; D017963:Azithromycin / Q000008:administration & dosage / Q000494:pharmacology*; D017291:Clarithromycin / Q000008:administration & dosage / Q000494:pharmacology; D018592:Cross-Over Studies; D004347:Drug Interactions; D004917:Erythromycin / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008874:Midazolam / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D000900:Anti-Bacterial Agents; D004917:Erythromycin; D017963:Azithromycin; D017291:Clarithromycin; D008874:Midazolam